chr6-106286165-C-T

Position:

• chr6-106286165-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004849.4(ATG5):​c.316-6342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,968 control chromosomes in the GnomAD database, including 13,678 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13678 hom., cov: 32)
• Consequence: ATG5 NM_004849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

Genes affected

ATG5 (HGNC:589): (autophagy related 5) The protein encoded by this gene, in combination with autophagy protein 12, functions as an E1-like activating enzyme in a ubiquitin-like conjugating system. The encoded protein is involved in several cellular processes, including autophagic vesicle formation, mitochondrial quality control after oxidative damage, negative regulation of the innate antiviral immune response, lymphocyte development and proliferation, MHC II antigen presentation, adipocyte differentiation, and apoptosis. Several transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ATG5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG5	NM_004849.4	c.316-6342G>A		intron_variant		ENST00000369076.8	NP_004840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG5	ENST00000369076.8	c.316-6342G>A		intron_variant		1	NM_004849.4	ENSP00000358072.3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63648 AN: 151850 Hom.: 13642 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.408

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.419 AC: 63746 AN: 151968 Hom.: 13678 Cov.: 32 AF XY: 0.424 AC XY: 31473 AN XY: 74282

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.407

Alfa AF: 0.380 Hom.: 23226

Bravo AF: 0.436

Asia WGS AF: 0.423 AC: 1468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs633724; hg19: chr6-106734040; COSMIC: COSV58350019; COSMIC: COSV58350019;